Biomarker panels for on-treatment prediction of response to immuno-oncology drugs

Abstract

Biomarker panels for the prediction of patient response to immunotherapy, and methods of use thereof.

What is claimed is: 
     
       1. A method comprising:
 obtaining an initial sample comprising blood from a human subject who has lung cancer; administering to the human subject at least one dose of an antibody that binds to programmed cell death protein 1 (PD-1) or an antibody that binds to programmed cell death 1 ligand 1 (PD-L1); 
 obtaining a subsequent sample of blood from the human subject; 
 measuring a level of interleukin 6 (IL-6) in the initial sample and the subsequent sample using an ultrasensitive protein detection technology; 
 comparing the levels of IL-6 in the initial sample and the subsequent sample; and 
 (a) administering to the human subject further doses of the antibody if the subsequent sample has decreased levels of IL-6 as compared to the initial sample, or 
 (b) administering to the human subject at least one therapy with or without further doses of the antibody if the subsequent sample has increased levels or no change in levels of IL-6 as compared to the initial sample. 
 
     
     
       2. The method of  claim 1 , wherein the therapy comprises administration of chemotherapy, radiotherapy, chemoradiotherapy, an immunotherapy not comprising the antibody administered in  claim 1 , and/or anti-angiogenic agents. 
     
     
       3. The method of  claim 1 , further comprising measuring and comparing the levels of C-reactive protein (CRP) or chemokine (C-X-C motif) ligand 10 (CXCL10) in the initial sample and the subsequent sample. 
     
     
       4. The method of  claim 1 , further comprising measuring and comparing the levels of CRP; of CRP, interleukin 10 (IL-10), interleukin 15 (IL-15), interleukin 17A (IL-17A), and CXCL10 in the initial sample and the subsequent sample. 
     
     
       5. The method of  claim 1 , further comprising measuring and comparing the levels of CRP, IL-8, IL-15, IL-17A, IL-2 Receptor alpha, and soluble CD137 in the initial sample and the subsequent sample. 
     
     
       6. The method of  claim 1 , further comprising measuring and comparing the levels of soluble T cell immunoglobulin-3 (Tim-3), Lymphocyte activation gene-3 (Lag-3), or IL-2 Receptor alpha in the initial sample and the subsequent sample. 
     
     
       7. The method of  claim 1 , wherein the ultrasensitive protein detection technology is a single molecule array digital ELISA. 
     
     
       8. The method of  claim 1 , wherein comparing the levels of IL-6 in the initial sample and the subsequent sample comprises determining ratios of the levels of IL-6 in the initial sample and the subsequent sample or determining percentage change between the levels of IL-6 in the initial sample and the subsequent sample. 
     
     
       9. The method of  claim 8 , further comprising determining an immuno-oncology (I-O) response score using the levels, or ratios or percentage change between the levels of IL-6 in the initial sample and the subsequent sample. 
     
     
       10. The method of  claim 9 , wherein determining an I-O response score comprises applying principal component analysis or linear regression algorithm. 
     
     
       11. The method of  claim 1 , wherein the sample comprises plasma or serum. 
     
     
       12. The method of  claim 1 , wherein the lung cancer is non-small-cell lung cancer (NSCLC). 
     
     
       13. The method of  claim 3 , further comprising measuring and comparing the levels of one or more of IL-10, IL-15, and IL-17A in the initial sample and the subsequent sample. 
     
     
       14. The method of  claim 4 , further comprising measuring and comparing the levels of IFNgamma in the initial sample and the subsequent sample. 
     
     
       15. The method of  claim 1 , wherein the method comprises administering to the human subject at least one dose of an antibody that binds to PD-1. 
     
     
       16. The method of  claim 15 , wherein the antibody is PF-06801591, AMP-224, BGB-A317, BI 754091, JS001, MEDI0680, PDR001, REGN2810, SHR-1210, TSR-042, pembrolizumab, nivolumab, or pidilizumab. 
     
     
       17. The method of  claim 1 , wherein the method comprises administering to the human subject at least one dose of an antibody that binds to PD-L1. 
     
     
       18. The method of  claim 17 , wherein the antibody is BMS-936559, FAZ053, KN035, Atezolizumab, Avelumab, or Durvalumab.